Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to test the hypothesis that target-cell activity influences the degree and time course of interleukin 1 beta (IL-1 beta)-mediated beta-cell impairment in vitro. Functional and morphological studies were performed in cultured newborn rat islets of Langerhans exposed from 6 h to 6 days to 50-2000 ng/L recombinant human IL-1 beta. Beta-Cell activity was modulated by glucose and nonglucose agents (15 mM L-leucine and 10 microM of long-acting somatostatin analogue SMS 201-995). In 11 mM glucose, 2000 ng/L of IL-1 beta caused inhibition of insulin release after approximately 6 h of exposure to IL-1 beta; in 3.3 mM glucose culture, onset of inhibition was delayed by this IL-1 beta concentration until after 48 h of exposure. Similarly, stimulation and suppression of beta-cell function with L-leucine and SMS 201-995, respectively, resulted in acceleration and delay of IL-1 beta-mediated inhibition. The dose-response curve of the IL-1 beta effect was shifted left- and rightward during high and low beta-cell activity, respectively. In analogy, increasing IL-1 beta concentration, exposure time, and beta-cell activity resulted in increasing islet disintegration. Thus, the resting beta-cell is more resistant to IL-1 beta-mediated impairment than the working beta-cell.
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PMID:Interaction of beta-cell activity and IL-1 concentration and exposure time in isolated rat islets of Langerhans. 267 56

We studied the extrapancreatic effects of L-leucine infusion (2.5 mumol/kg/min) in six controls (three females, three males) and three members of a family with leucine-sensitive hypoglycemia (LSH). Total glucose disposal and endogenous glucose production (EGP) rates were assessed after an overnight fast (12 to 14 hour) during somatostatin (SRIF) infusion (500 micrograms/h) with insulin replacement (0.2 mU/kg/min), combined with D-(3-3H)-glucose infusion. Additional studies of forearm arterial-venous (A-V) balances of amino acids, glucose, and other substrates, combined with L-(1-14C)-leucine kinetics, were done in these two groups. L-leucine infusion resulted in a 15% decrease in whole-body total glucose utilization in controls (P less than .05) during SRIF-insulin infusion, but did not affect glucose utilization in LSH subjects. EGP was not affected by L-leucine infusion in either group. Control subjects demonstrated a significant reduction in forearm glucose uptake and greater lactate release during L-leucine infusion, compared to the basal state. In contrast, subjects with LSH showed a slight increase in forearm glucose uptake and significantly less lactate release during L-leucine infusion. Subjects with LSH demonstrated significantly lower forearm leucine uptake, and lower rates of appearance and oxidation of L-(1-14C)-leucine during leucine infusion, compared to controls. Our data suggest that members of this LSH kindred have a defect in intracellular leucine metabolism in skeletal muscle, resulting in a lack of leucine-induced inhibition of glucose utilization. This may contribution to the development of hypoglycemia in these subjects.
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PMID:Extrapancreatic effects of L-leucine infusion in leucine-sensitive and control subjects. 288 10

We have evaluated the potential of the clonal insulin-secretory cell line HIT-T15 as a model system for investigating stimulus-secretion coupling in pancreatic B cells. In contrast to other cell lines, HIT cell insulin secretion was consistently stimulated 2- to 3-fold by D-glucose. The maximally effective concentration of glucose was 10 mmol/l; between 2 and 10 mmol/l glucose the increase in insulin release was paralleled by an increased rate of glucose oxidation. The main characteristics of glucose-stimulated insulin release by HIT cells were essentially similar to those of normal islets. Thus, the response was specific for metabolizable sugars (D-mannose and D-glyceraldehyde stimulated insulin release but L-glucose and D-galactose were ineffective); markedly dependent on extracellular Ca2+ concentration; potentiated by forskolin, glucagon, acetylcholine and 12-O-tetradecanoyl phorbol 13-acetate; inhibited by adrenaline or somatostatin; showed a biphasic pattern of release in perifusion experiments, with both phases being potentiated by forskolin. The secretory response of the HIT cells to amino acids was also similar to that of normal islets. Thus, L-leucine and its deamination product 2-ketoisocaproate were effective stimuli, whereas L-isoleucine and L-glutamine were ineffective. Insulin release from HIT cells could also be evoked by the sulphonylureas glibenclamide and tolbutamide and by an increase in concentration of extracellular K+ to 40 mmol/l. The content of cyclic AMP in HIT cells was increased modestly by glucose but not by an increase in extracellular K+. Forskolin elicited a 4-fold increase in cyclic AMP content. We conclude that HIT cells retain the essential features of the insulin secretory response of normal B cells and represent an important tool for further biochemical characterization of the secretory system.
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PMID:Insulin secretory responses of a clonal cell line of simian virus 40-transformed B cells. 302 78

Conflicting reports on the direction and magnitude of the effect of somatostatin on (pro)insulin synthesis prompted our investigation. Two assays for proinsulin synthesis were designed in which [4,5-3H]-L-leucine incorporation into proinsulin was normalized on the basis of postincubation insulin levels rather than on the number of islets incubated. Somatostatin at a concentration of 10 micrograms/ml inhibited 300 mg/dl glucose-stimulated proinsulin synthesis by 25% from 448 +/- 25 dpm/microunits insulin to 336 +/- 25 dpm/microunits insulin (disintegrations per minute in the proinsulin peak per microunit extractable insulin) (p less than 0.05). Glucagon (10 micrograms/ml) reversed the inhibitory effect of somatostatin on proinsulin synthesis from 336 +/- 25 dpm/microunits insulin to 480 +/- 44 dpm/microunits insulin (p less than 0.02). Somatostatin (10 micrograms/ml) had no significant effect on proinsulin synthesis in the presence of 70 mg/dl or 150 mg/dl glucose. Insulin release in 300 mg/dl glucose was inhibited 38% by 10 micrograms/ml somatostatin from 3.05 +/- 0.40 mU medium/mU tissue to 1.90 +/- 0.10 mU medium/mU tissue (p less than 0.01) over a 45-minute incubation period. These data suggest that somatostatin may act on glucose signal transduction on a level at which both insulin synthesis and secretion are affected. Further, the results are consistent with the hypothesis that cyclic AMP participates in mediating somatostatin effects on B-cell metabolism.
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PMID:Evidence that somatostatin inhibits proinsulin synthesis and insulin release by isolated pancreatic islets of the rat. 610 96

Isolated perfused rat pancreases were exposed, in the presence of 10. 0 mM L-leucine, to either alpha-D-glucose pentaacetate, beta-L-glucose pentaacetate, or unesterified D-glucose, all tested at a 1.7 mM concentration. The pentaacetate ester of alpha-D-glucose and, to a lesser extent, that of beta-L-glucose stimulated both insulin and somatostatin release, whereas unesterified D-glucose failed to do so. In the case of insulin output, the two esters differed from one another not solely by the magnitude of the secretory response but also by its time course and reversibility. Compared with these data, the most salient difference found in the case of somatostatin release consisted of the absence of an early secretory peak in response to alpha-D-glucose pentaacetate administration and the higher paired ratio between the secretory responses evoked by the esters of glucose and by unesterified D-glucose (5.5 mM) administered at the end of the experiments. The two esters provoked an initial and short-lived stimulation of glucagon secretion, in sharp contrast to the immediate inhibitory action of unesterified D-glucose. Thereafter, alpha-D-glucose pentaacetate, but not beta-L-glucose pentaacetate, caused inhibition of glucagon release, such an effect being reversed when the administration of the ester was halted. These findings indicate a dual mode of action of glucose pentaacetate esters on hormonal secretion from the endocrine pancreas. The intracellular hydrolysis of alpha-D-glucose pentaacetate and subsequent catabolism of its hexose moiety may contribute to the early peak-shaped insulin response to this ester, to the persistence of a positive secretory effect in B and D cells after cessation of its administration, and to the late inhibition of glucagon release. However, a direct effect of the esters themselves, by some as-of-yet unidentified coupling process, is postulated to account for the stimulation of insulin and somatostatin release by beta-L-glucose pentaacetate and for the initial enhancement of glucagon secretion provoked by both glucose esters.
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PMID:Dual mode of action of glucose pentaacetates on hormonal secretion from the isolated perfused rat pancreas. 975 79

Enhanced protein synthesis in skeletal muscle after ingestion of a balanced meal in postabsorptive rats is mimicked by oral leucine administration. To assess the contribution of insulin to the protein synthetic response to leucine, food-deprived (18 h) male rats (approximately 200 g) were intravenously administered a primed-constant infusion of somatostatin (60 microg + 3 microg.kg(-1).h(-1)) or vehicle beginning 1 h before administration of leucine (1.35 g L-leucine/kg) or saline (control). Rats were killed 15, 30, 45, 60, or 120 min after leucine administration. Compared with controls, serum insulin concentrations were elevated between 15 and 45 min after leucine administration but returned to basal values by 60 min. Somatostatin maintained insulin concentrations at basal levels throughout the time course. Protein synthesis was increased between 30 and 60 min, and this effect was blocked by somatostatin. Enhanced assembly of the mRNA cap-binding complex (composed of eukaryotic initiation factors eIF4E and eIF4G) and hyperphosphorylation of the eIF4E-binding protein 1 (4E-BP1), the 70-kDa ribosomal protein S6 kinase (S6K1), and the ribosomal protein S6 (rp S6) were observed as early as 15 min and persisted for at least 60 min. Somatostatin attenuated the leucine-induced changes in 4E-BP1 and S6K1 phosphorylation and completely blocked the change in rp S6 phosphorylation but had no effect on eIF4G small middle dot eIF4E assembly. Overall, the results suggest that the leucine-induced enhancement of protein synthesis and the phosphorylation states of 4E-BP1 and S6K1 are facilitated by the transient increase in serum insulin. In contrast, assembly of the mRNA cap-binding complex occurs independently of increases in insulin and, by itself, is insufficient to stimulate rates of protein synthesis in skeletal muscle after leucine administration.
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PMID:Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine. 1193 75